The overall goal of this program is to investigate the genetic basis of taste-guided behavior in Drosophila melanogaster. We are broadly interested in genes that can directly impact complex behaviors. Drosophila are a highly successful model for the molecular dissection of behavior, and ingestive behavior promises to be very applicable to this analysis. We will use novel methods and animal psychophysical approaches to map genetically a range of taste and ingestion phenotypes exhibited by Drosophila. The fruit fly has a well- organized visual and chemosensory nervous system and a complex behavioral repertoire. Its molecular and behavioral aspects of taste are very similar to humans. In the proposed research, we will test four high potency sweeteners and two natural saccharides to help elucidate how the taste system works. We will behaviorally phenotype inbred wild-caught fly lines for stimuli not typically tested in flies such as the high potency sweeteners Na saccharin, Na cyclamate, sucralose, neohesperidin dihydrochalcone (NHDC), in addition to more traditional saccharides, such as fructose and maltose. The use of high potency sweeteners with flies can increase the range of taste genes revealed in our assays, as the use of Na saccharin did in mice. Our present goals are to elucidate the range of taste responses of Drosophila, to find quantitative trait loci (QTL) that influence taste behavior, and to sequence the Gr5a cluster of related taste receptor genes to look for polymorphisms. The use of QTL analysis enables the potential discovery of many types of genetic bases of variability and not only variation in receptor genes. The application of QTL analysis to taste-guided behavior in flies has not been previously undertaken. The ability to perceive the taste quality of a food source is critical for survival and is genetically highly polymorphic in most animals examined to date. Discrimination between nutritious and toxic substances leads to the acceptance or rejection of a potential food source, respectively. This discrimination is based on the perceived taste quality of that food source. The insect Drosophila melanogaster has taste responses very similar to those of humans and other mammals. Carbohydrates are a major food source for both mammals and flies, while many of the chemicals toxic to mammals are also avoided by flies. Drosophila sensitivity ranges for taste stimuli are within the perceived concentration ranges of humans. The Aims of this proposal focus on (1) looking at the responses of wild-caught inbred flies to a variety of "sweeteners" to isolate extreme phenotypes. Fly lines with extreme phenotypes from Aim 1 will be used in (2a) QTL analysis to find genes that affect taste behavior. We concentrate on receptor genes in (2b), sequencing putative sweet receptor genes homologous to the trehalose receptor gene Gr5a, in order to look for polymorphisms associated with sweetener phenotypes. This program will help elucidate genetic variation that causes variation in taste perception and feeding. Taste perception and concomitant ingestive behavior (energy balance) is one of the most fundamental behavioral systems in biology, the other being reproduction. Today, we understand that genes can play a major role in determining individual behavior, even in humans. Since the fruit fly is the best genetic model of behavior and also happens to be omnivorous, like humans, we propose to uncover genes that underlie taste perception and ingestion using Drosophila melanogaster as a quantitative genetic model. Understanding the physiological and molecular basis of taste and ingestive behavior is essential to understanding human eating and energy disorders. [unreadable] [unreadable] [unreadable]